Neurophysiology of Pain in Children with Cerebral Palsy

项目总结/摘要 脑性瘫痪（CP）是在美国诊断的最普遍和最昂贵的儿科神经系统疾病之一。 美国的虽然这些儿童的脑损伤是非渐进性的，但它们往往会引发一种 结构的级联（即，骨骼排列不正，肌肉挛缩）和功能性（即，共同收缩， 肌肉骨骼系统内的异常，在整个发育过程中会变得更糟。 这些继发性变化被认为是慢性肌肉骨骼疼痛的主要原因， 在很大比例的脑瘫儿童中可见。然而，目前在这方面缺乏知识。 区域，特别是关于持续性疼痛的神经生理学机制，因为迄今为止的大多数研究 集中在量化疼痛症状的流行，而不是潜在的生理。没有这个 关键信息，慢性肌肉骨骼疼痛的预防，治疗和评估将无法推进。 我们广泛的脑磁图（MEG）脑成像程序已经确定，早期脑损伤 CP儿童所经历的各种症状导致躯体感觉对外周感觉的异常处理 皮质最近，我们扩展了这些结果，表明患有CP的儿童， 足部外周刺激后的体感皮层振荡也具有较高的疼痛报告。 这种关系意味着躯体感觉系统的完整性与 脑性瘫痪儿童的皮层加工和痛觉。这项提案的目的是测试我们的 一个科学前提是，躯体感觉神经连接受到干扰，可能是由于适应不良造成的， 早期脑损伤后的神经可塑性变化，在CP儿童中发生改变，这导致 疼痛感知网络和慢性疼痛的活动增强。我们的方法是“高风险”的，但有 潜在的是非常“有益的”，因为它可能会导致新的见解和范式转变，我们的理解， 脑瘫儿童的疼痛感知本提案的具体目标是：（1）证明 体感皮层振荡的机械和伤害感受器的外周刺激后， 脚和手将规模与儿童的感知疼痛水平，和（2）确定是否强度的躯体感觉 外周刺激后的皮层振荡在CP儿童中有不同的改变， 与高疼痛水平相比，以及两组是否与典型发育（TD）儿童不同。简而言之，我们的研究 将使用MEG，先进的图像重建方法和时间序列分析来量化 TD儿童外周机械感受器和伤害感受器刺激后体感皮层振荡， 以及患有痉挛性双瘫CP和不同疼痛水平的儿童（即，严重性）。实现我们的目标将提供 对CP儿童慢性疼痛的神经基础有了实质性的了解，并可能引发CP治疗的范式转变。 在该人群中进行肌肉骨骼疼痛的主流治疗和评估。

PROJECT SUMMARY/ABSTRACT Cerebral palsy (CP) is one of the most prevalent and costly pediatric neurologic conditions diagnosed in the United States. Although the brain injuries seen in these children are non-progressive, they often instigate a cascade of structural (i.e., boney malalignments, muscular contractures) and functional (i.e., co-contractions, spasticity) abnormalities within the musculoskeletal system that can become worse throughout development. These secondary changes are presumed to be primarily responsible for the chronic musculoskeletal pain that is seen in a large percentage of children with CP. However, currently there is a major lack of knowledge in this area, especially in regard to the neurophysiological mechanisms of the persistent pain, as most studies to date have focused on quantifying the prevalence of pain symptoms and not the underlying physiology. Without this critical information, the prevention, treatment and evaluation of the chronic musculoskeletal pain will not advance. Our extensive magnetoencephalographic (MEG) brain imaging program has identified that the early brain insults experienced by children with CP result in aberrant processing of the peripheral sensations by the somatosensory cortices. Recently, we have extended these results by showing that children with CP who have more abnormal somatosensory cortical oscillations following peripheral stimulation of the feet, also have higher reported pain. This relationship implies that there might be a fundamental link between the integrity of somatosensory cortical processing and the pain perceptions of children with CP. The goal of this proposal is to test our scientific premise that the disturbed somatosensory neural connections, potentially arising from maladaptive neuroplastic changes following early brain injuries, are altered in children with CP and that this leads to heightened activity in the pain perception network and chronic pain. Our approach is of “high risk”, but has the potential to be remarkably “rewarding,” as it may lead to novel insights and a paradigm shift in our understanding of pain perception in children with CP. The Specific Aims of this proposal will (1) demonstrate that the strength of somatosensory cortical oscillations following peripheral stimulation of the mechano- and nociceptors of the feet and hands will scale with a child’s perceived pain levels, and (2) determine if the strength of somatosensory cortical oscillations following peripheral stimulation are differentially altered in children with CP who have low versus high pain levels, and whether both groups differ from typically-developing (TD) children. Briefly, our study will use MEG, advanced image reconstruction methods, and time series analysis to quantify the strength of somatosensory cortical oscillations following stimulation of peripheral mechano- and nociceptors in TD children, and children who have spastic diplegic CP and different pain levels (i.e., severity). Achieving our Aims will provide substantial insight on the neural basis of chronic pain in children with CP, and may spark a paradigm shift in the mainstream treatment and assessment of musculoskeletal pain in this population.